The present invention, in some embodiments thereof, relates to conditioning protocols and to the use of same for tissue regeneration.
Pancreatic diseases such as diabetes, pulmonary diseases such as COPD, cystic fibrosis, emphysema, pulmonary fibrosis or pulmonary hypertension, liver diseases such as liver cirrhosis or viral liver diseases (e.g. Hepatitis B or C), heart diseases such as heart failure, and kidney diseases such as kidney failure are diseases of great medical and economic impact for which no satisfactory/optimal treatments are available. Most currently available therapies only slightly improve the quality of life for the patients in need. At present, the only definitive treatment for end-stage lung disease, liver disease, heart disease and kidney disease is the replacement of the damaged organ, but many patients die while on the waiting list due to a severe shortage of organs for transplantation and the limit for inscription being often set at 60 years of age.
Transplantation of fully differentiated haplotype-matched grafts from donors is a life-saving, medical procedure of choice for replacing injured or diseased organs such as pancreas, heart, liver or lung. Such a treatment modality, however, suffers from considerable disadvantages. Allogeneic transplantation of organs/tissues is impossible to implement in a great many cases due to the lack of organ donors (e.g. usually cadavers) and the unavailability of suitable immunologically matched organ donors. Furthermore, the use of living human donors often presents health risks and ethical dilemmas. Thus, large numbers of patients who would otherwise benefit from therapeutic transplantation succumb to diseases associated with pancreatic, liver, lung, kidney and pulmonary failure while awaiting matched transplant donors.
Thus, in view of the unique potential curative benefits of transplantation therapy, there is clearly an urgent and longstanding need for non-syngeneic donor-derived pancreatic, liver, lung, kidney and pulmonary organs/tissues which can be obtained in sufficient quantities, and which can be optimally tolerated immunologically, so as to render feasible the routine and optimally effective therapeutic transplantation of such organs/tissues.
One strategy, which has been proposed to fulfill this aim involves using gestational stage grafts for transplantation.
Additional background art includes:
PCT Publication No. WO2006/038211 relates to methods of providing a pancreatic, lymphoid/hematopoietic or pulmonary organ and/or tissue function to a mammalian subject. The method comprising transplanting into the subject a developing mammalian pancreatic, lymphoid/hematopoietic or pulmonary organ/tissue graft, respectively. The pulmonary graft disclosed in WO 2006/038211 is at a developmental stage essentially corresponding to that of a porcine pulmonary organ/tissue at a gestational stage selected from a range of about 42 to about 80 days of gestation.
PCT Publication No. WO 2004/078022 relates to methods of treating a disorder associated with pathological organ or tissue physiology or morphology. The method is effected by transplanting into a subject a mammalian organ or tissue graft (e.g. renal, pancreatic, hepatic, cardiac or lymphoid organ or tissue graft) selected not substantially expressing or presenting at least one molecule capable of stimulating or enhancing an immune response in the subject.
Another strategy, which has been proposed to fulfill this aim involves using isolated populations of cells, such as hepatocytes, hematopoietic progenitor cells and stem cells (e.g. cord blood and bone marrow).
PCT Publication No. WO 2013/084190 relates to a pharmaceutical composition comprising as an active ingredient an isolated population of cell suspension from a mammalian fetal pulmonary tissue. The fetal pulmonary tissue is at a developmental stage corresponding to that of a human pulmonary organ/tissue at a gestational stage selected from a range of about 20 to about 22 weeks of gestation. Methods of using the pharmaceutical composition are also disclosed.